Cell Proliferation in Precancerous Liver: Relation to Presence and Dose of Carcinogen2

Abstract

The precancerous period in the livers of rats fed 2-acetylaminofluorene is divisible into two phases. During the first 4 to 8 weeks no significant change in the total number of liver cells occurs; thereafter the total number of liver cells increases at a constant rate. In the present study, when the rate of this constant cell proliferation was plotted against the relative dose of the carcinogen, the points approximated a function describing the properties of a first-order chemical reaction. When administration of the carcinogen was discontinued, the cell proliferation stopped after a short delay. These two findings considered together demonstrate a physiological relationship between the presence of the carcinogen and the preneoplastic cell proliferation in the target organ. It is suggested that the preneoplastic cell proliferation is a form of compensatory hyperplasia in response to the inactivation of some subcellular liver constituent, which is essential to life and is replaced only in association with cell division, and that this inactivation is accomplished by a first-order chemical reaction between the carcinogen and the essential cell constituent.